Lack of severe malformations versus occurrence of marked embryotoxic effects after treatment of pregnant mice with cis-platinum.

The embryotoxic and teratogenic effects caused by the inorganic cytostatic drug cis-diamminedichloroplatinum(II) ("cis-platinum") were investigated in mice. Single doses of 2.5, 5, 10 or 20 mg cis-platinum/kg were administered to pregnant mice on day 8, 10, 12, 14 or 16 of pregnancy; on day 18, all fetuses were removed and examined for toxic phenomena and for external, skeletal and internal malformations. A dose-dependent reduction of the number of fetuses per litter, a decrease of fetal body weight, and a marked retardation of skeletal ossification processes reflected the severe embryolethal and embryotoxic influence of cis-platinum; this influence was most pronounced when the drug was applied during organogenesis, i.e. on day 8, 10 or 12 of murine pregnancy. In contrast, the incidence of malformations was surprisingly rare after treatment with cis-platinum: Neither external nor skeletal malformations appeared more frequently than in control populations; most fetal internal organs were without anomalies, however, a portion of 10-20% of the fetuses exhibited slight signs of hydrocephaly after application of cis-platinum on day 12.